Over this period, our work has concentrated on the role of members of the c-src family of protooncogenes in the development of human malignancies and the identification and characterization of other gene products associated with the progression of human breast or colon carcinoma. This research can be subdivided into several projects. 1. Characterization of human protooncogenes in the c-src family. c-src, the protooncogene homolog of the Rous sarcoma virus oncogene v-src, is the prototypic member of a family of genes that encode membrane-bound, N-terminal myristylated, tyrosine protein kinases. The group, of which seven members have been identified, is characterized by highly conserved genes with common intron-exon structures, all encoding membrane bound, N-terminal myristylated tyrosine protein kinases of molecular weight 56-60 Kd. Although three members of this family, src, yes, and fgr, were originally isolated as the transforming genes of RNA tumor viruses, there has been little evidence associating these gene products with human tumors. Our previous work has concentrated on defining the role of the c-src protooncogene in human tumors. We have shown that the c-src protein product (pp60c-src) is specifically overexpressed in all normal and neoplastic tissues and cell lines of neuroectodermal origin that retain a neuronal phenotype. When immature neuroblastomas are differentiated in cell culture toward a neuronal pattern of cellular functions, there is an attendant increase in pp60c-src expression and total activity. As there is no obvious difference in expression between neuroblastoma and normal brain and no elevation of the specific activity of neural pp60c-src, this phenomenon is felt to be a marker of neural differentiation, rather than transformation of these cells.